title: Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen receptor-alpha.
abstract: Breast cancer is the most common hormone-dependent malignancy in women. Homeobox (HOX) transcription factors regulate many cellular functions, including cell migration, proliferation and differentiation. The aberrant expression of HOX genes has been reported to be associated with human reproductive cancers. Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER-beta, are known to play critical roles in the regulation of breast cancer cell growth. However, an understanding of the potential relationship between HOXA7 and ER in breast cancer cells is limited. In this study, our results demonstrate that knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and ERα expression. In addition, HOXA7 knockdown attenuated E2-induced cell proliferation as well as progesterone receptor (PR) expression. The stimulatory effects of E2 on cell proliferation and PR expression were abolished by co-treatment with ICI 182780, a selective ERα antagonist. In contrast, overexpression of HOXA7 significantly stimulated cell proliferation and ERα expression. Moreover, E2-induced cell proliferation, as well as PR expression, was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic role for HOXA7 in modulating breast cancer cell proliferation via regulation of ERα expression. This finding contributes to our understanding of the role HOXA7 plays in regulating the proliferation of ER-positive cancer cells.
authors.affiliation: Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China; Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jung-Chien
authors.initials: JC
authors.lastname: Cheng
authors.forename: He-Feng
authors.initials: HF
authors.lastname: Huang
authors.forename: Peter C K
authors.initials: PC
authors.lastname: Leung
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005260:Female; D000077267:Fulvestrant; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D061986:MCF-7 Cells; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: C506487:ESR1 protein, human; C490918:ESRRB protein, human; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; C115962:HOXA7 protein, human; D018398:Homeodomain Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000077267:Fulvestrant; D004958:Estradiol
keywords: Breast cancer; Estrogen receptor; HOX